PMID- 18180378
OWN - NLM
STAT- MEDLINE
DCOM- 20080425
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 111
IP  - 6
DP  - 2008 Mar 15
TI  - Targeting dendritic cell signaling to regulate the response to immunization.
PG  - 3050-61
LID - 10.1182/blood-2007-11-122408 [doi]
AB  - Dendritic cells (DCs) are key regulators of the immune system; they capture 
      antigens and then can either stimulate an immune response or induce tolerance. 
      Our aim was to activate individual DC signaling pathways to regulate the immune 
      response. We therefore expressed constitutive activators of mitogen-activated 
      protein kinase (MAPK) pathways or the interferon pathway, together with tumor 
      antigens, using lentivectors. Triggering of p38 activated DCs substantially 
      enhanced the antitumor immune response and prolonged survival of tumor-bearing 
      mice. Activation of extracellular signal-regulated kinase (ERK) increased 
      TGF-beta expression while expression of a constitutively activated interferon 
      regulatory factor-3 (IRF3) stimulated IL-10 secretion by DCs. ERK and IRF3 
      suppressed the immune response and stimulated expansion of regulatory T cells. 
      These results provide a toolkit to regulate immune responses to viral vector or 
      DC immunization; vaccine responses to foreign or tumor antigens can be enhanced 
      and harmful responses to self-antigens or introduced transgenes can be reduced.
FAU - Escors, David
AU  - Escors D
AD  - Infection and Immunity, University College London, London, United Kingdom.
FAU - Lopes, Luciene
AU  - Lopes L
FAU - Lin, Rongtuan
AU  - Lin R
FAU - Hiscott, John
AU  - Hiscott J
FAU - Akira, Shizuo
AU  - Akira S
FAU - Davis, Roger J
AU  - Davis RJ
FAU - Collins, Mary K
AU  - Collins MK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080107
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Cytokines)
RN  - 0 (Interferon Regulatory Factor-3)
RN  - 0 (Irf3 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/immunology
MH  - Cell Line
MH  - Cytokines/biosynthesis/metabolism
MH  - Dendritic Cells/cytology/*immunology/metabolism
MH  - Enzyme Activation
MH  - Genetic Vectors/genetics
MH  - Humans
MH  - *Immunization
MH  - Interferon Regulatory Factor-3/metabolism
MH  - Lentivirus/genetics
MH  - Mice
MH  - Mitogen-Activated Protein Kinases/genetics/immunology/metabolism
MH  - Myeloid Differentiation Factor 88/metabolism
MH  - Neoplasms/enzymology/genetics/immunology
MH  - Phenotype
MH  - Sensitivity and Specificity
MH  - Signal Transduction/*immunology
MH  - Up-Regulation
EDAT- 2008/01/09 09:00
MHDA- 2008/04/26 09:00
CRDT- 2008/01/09 09:00
PHST- 2008/01/09 09:00 [pubmed]
PHST- 2008/04/26 09:00 [medline]
PHST- 2008/01/09 09:00 [entrez]
AID - S0006-4971(20)48614-8 [pii]
AID - 10.1182/blood-2007-11-122408 [doi]
PST - ppublish
SO  - Blood. 2008 Mar 15;111(6):3050-61. doi: 10.1182/blood-2007-11-122408. Epub 2008 
      Jan 7.